P. Tosi et al., REDUCTION OF HEAT-SHOCK-PROTEIN-70 AFTER PROLONGED TREATMENT WITH RETINOIDS - BIOLOGICAL AND CLINICAL IMPLICATIONS, American journal of hematology, 56(3), 1997, pp. 143-150
Heat shock proteins (HSPs) are a group of highly conserved polypeptide
s involved in cellular response to heat or other physical or chemical
stresses. It has been recently reported that HSPs could play a role in
cellular differentiation. In this study we have evaluated, by a cytof
luorimetric method, the presence of HSP-70 in HL-60 cells during treat
ment with all-trans retinoic acid (ATRA), g-cis retinoic acid (g-cis R
A), and 13-cis retinoic acid (13-cis RA). After 1 and 3 days of incuba
tion at 10(-7) M, HSP-70 did not show any Variation compared to contro
l; prolonging the exposure, together with the appearance of cellular d
ifferentiation along the granulocytic pathway and apoptosis, a progres
sive decrease of HSP-70 was observed that, after 8 days of treatment,
was reduced by 40% with ATRA and by 28% with 9-cis RA compared to untr
eated samples, while only minimal changes were evident by incubating t
he cells with 13-cis RA, Reduction of HSP-70 was not associated with d
ecreased protein synthesis, as demonstrated by [H-3] leucine incorpora
tion. Double labeling with propidium iodide showed a decrease in HSP-7
0 in all the phases of the cell cycle concomitant with a reduced perce
ntage of cycling cells in ATRA-treated samples. Dot blot and Northern
blot analysis demonstrated no change in HSP-70 mRNA after retinoid tre
atment, thus suggesting a post-transcriptional regulation of the pheno
menon. This reduced production of HSP-70 caused by ATRA and by g-cis R
A, though to a lesser extent, could render the cells more sensitive to
cytotoxic agents and could provide the rationale for the efficacy of
ATRA + chemotherapy combinations. (C) 1997 Wiley-Liss, Inc.